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Title Development of the Interrupted Nazarov Cyclization of Allenyl Vinyl Ketones, with Application to the Total Synthesis of the Cyclooctane Natural Product Roseadione
Publication Date
Degree PhD
Discipline/Department Department of Chemistry
Degree Level doctoral
University/Publisher Dalhousie University
Abstract The development of the interrupted Nazarov cyclization of allenyl vinyl ketones is presented. The intermediate oxyallyl cation, derived from an allenyl vinyl ketone, may be trapped efficiently by a divergent array of nucleophilic species generating functionalized cyclopent-2-enone products. Allenyl vinyl ketones are also a versatile source of cyclic molecules via a tandem reaction sequence terminated via reaction with acyclic dienes, cyclic dienes, aza-heterocycles, electron-rich alkenes, or styrenes by the formation of an additional ring by a [4 + 3] and/or [3 + 2] cyclization or by the formation of one additional carbon-carbon bond. The bicyclic compounds generated by these processes are densely substituted, and would be difficult to access as succinctly in other ways. The products of these interrupted Nazarov reactions generally reflect excellent regio- and stereoselectivity in the trapping reaction. In some instances, equilibrating conditions were shown to enhance the proportion of one product at the expense of another or to provide a different carbon skeleton. This process appears fairly general, and can be conducted with unsubstituted or alkyl, aromatic, or heteroaromatic allenyl vinyl ketones. The exceptional affinity of allenyl vinyl ketones to undergo interrupted Nazarov reactions is likely a result of the increased longevity of the intermediate oxyallyl cation, due in part to the increased resonance stabilization provided by the allene unit. The high regioselectivity noted in the trapping process was computationally and experimentally confirmed to be a result of a localization of the positive charge in the intermediate oxyallyl cation. The application of this recently developed methodology towards the synthesis of the natural product (+)-roseadione is also described. The tandem Nazarov/[4 + 3] cascade of allenyl vinyl ketones provides a unique manner in which to access the tricyclic core of this cyclooctanoid natural product, a molecule which, to date, has never been synthesized.
Subjects/Keywords Allenes; Allenyl Vinyl Ketones; Interrupted Nazarov Reactions; Oxyallyl Cations; [4 + 3] Cyclizations; [3 + 2] Cyclizations; Bicyclic Ring Systems; Eight Membered Ring Systems
Contributors Dr. Louis Barriault (external-examiner); Dr. Mark Stradiotto (graduate-coordinator); Dr. David L. Jakeman (thesis-reader); Dr. Ian R. Pottie (thesis-reader); Dr. Laura Turculet (thesis-reader); Dr. D. Jean Burnell (thesis-supervisor); Not Applicable (ethics-approval); Not Applicable (manuscripts); Not Applicable (copyright-release)
Language en
Country of Publication ca
Format application/pdf
Record ID handle:10222/13885
Other Identifiers TC-NSHD-13885
Repository canada
Date Indexed 2017-01-03
Grantor Dalhousie University

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